Remote imaging of single cell 3D morphology with ultrafast coherent phonons and their resonance harmonics

Abstract

Cell morphological analysis has long been used in cell biology and physiology for abnormality identification, early cancer detection, and dynamic change analysis under specific environmental stresses. This work reports on the remote mapping of cell 3D morphology with an in-plane resolution limited by optics and an out-of-plane accuracy down to a tenth of the optical wavelength. For this, GHz coherent acoustic phonons and their resonance harmonics were tracked by means of an ultrafast opto-acoustic technique. After illustrating the measurement accuracy with cell-mimetic polymer films we map the 3D morphology of an entire osteosarcoma cell. The resulting image complies with the image obtained by standard atomic force microscopy, and both reveal very close roughness mean values. In addition, while scanning macrophages and monocytes, we demonstrate an enhanced contrast of thickness mapping by taking advantage of the detection of high-frequency resonance harmonics. Illustrations are given with the remote quantitative imaging of the nucleus thickness gradient of migrating monocyte cells.

Changes in intra-nuclear mechanics in response to DNA damaging agents revealed by time-domain Brillouin micro-spectroscopy

“…This spreading reveals an increase in the roughness of the nucleus surface. The B-POM has already proved its capability to measure greater nucleus roughness for abnormal cells than for healthy cells [36] . Nuclear herniations and blebbing are indeed cell phenotypes that have long been considered for some cancer diagnosis and for tumor grading [7] , [37] .…”

Correlative Imaging of Motoneuronal Cell Elasticity by Pump and Probe Spectroscopy

“…The oscillating response of the sample reflectivity resulting from the interaction between light and the acoustic pulse propagating into the cell, usually called the Brillouin oscillations (BO) has demonstrated ability to map elasticity in biological cells. In-plane or in-depth investigations [10,11,12,13,14] can reveal the internal elasticity gradient and thickness of the cell. Such all optical technique is very convenient to design specific environment allowing the study of living cells [15,16].…”

3D phonon microscopy with sub-micron axial-resolution

“…If the measured volume is not homogeneous, then f B is a function of time where the spatial location of such variations is given by the speed of sound z = ν/t . Hence, resolving temporal variations of f B enables in-depth imaging 23,28 .…”